Core Viewpoint - The article discusses the Warburg effect, highlighting how cancer cells exhibit increased glycolysis even in the presence of oxygen, leading to enhanced lactate production and cancer progression. Recent research has uncovered the molecular mechanisms behind this phenomenon, specifically focusing on the role of lactate in activating the ERK signaling pathway through a lactylation-phosphorylation loop involving the enzyme GCN5 [2][3][5][7]. Group 1 - The Warburg effect describes the phenomenon where cancer cells maintain high levels of glycolysis despite sufficient oxygen, which is contrary to normal cellular metabolism [2]. - A recent study published in Nature Chemical Biology reveals that lactate promotes tumor progression by inducing lactylation of the ERK protein, enhancing the RAS-ERK signaling pathway [3][5]. - The study identifies GCN5 as the lactyltransferase responsible for ERK lactylation, which is activated by ERK phosphorylation, creating a positive feedback loop that amplifies lactate-driven cancer progression [5][7]. Group 2 - The research demonstrates that lactate-induced ERK lactylation weakens its interaction with MEK, promoting ERK dimerization and activation, which further drives cancer development [5][7]. - A cell-penetrating peptide was developed to specifically inhibit ERK lactylation, showing potential in suppressing tumor growth in KRAS mutant cancer models [5][7].